Competitive Inhibition
Carey Witkov___________________________
Objectives
The student will:
Topics
Tools
Background
Molecules that have similar shape can compete for receptor sites in a cell. Only that portion of the molecules that bind with the receptor site need be similar in shape. Examples of molecular pairs that exhibit competitive inhibition are:
1. Para-amino-benzoic-acid (PABA) and sulfanilamide
PABA is a precursor of folic acid, needed for bacterial growth. Sulfanilamide blocks the PABA membrane binding sites, acting as a bacteriostatic agent (e.g., an antibiotic, one of the sulfa drugs).
2. Serotonin (5-HT) and d-Lysergic Acid Diethylamide-25 (LSD)
Serotonin is a neurotransmitter in the brain that can be competitively inhibited by LSD resulting in a variety of disturbances in neural transmission and perceptual distortions.
3. Succinate dehydrogenase and malonate
Succinate dehydrogenase, a citric acid cycle enzyme that functions to convert succinate to fumarate is competitively inhibited by malonate, which structurally resembles succinate but cannot be dehydrogenated. The effectiveness of malonate in competitively inhibiting succinate dehydrogenase strongly suggests that the enzyme's substrate-binding site is designed to bind both of the substrate's carboxylate groups, presumably through the influence of two appropriately placed positively charged residues.
Let's Begin1. The Berkeley enhancement of RASMOL (RASMOL2.6-ucb), a public domain pdb file viewer allows viewing more than one molecule simultaneously.
2. Open the first pair of molecules and determine which regions of the molecules are probably involved in competing for binding sites.
3. How large are the regions of similar shape? One measure of size for the common regions is the number of atoms in the regions. Another measure are the actual X-Y-Z linear dimensions (e.g., in angstroms) of the regions. Use RASMOL's bond-distance measurement capability to estimate the actual lengths of the sides of the regions.
4. Repeat #2 for the other pair of molecules.
5. Were the sizes of the common regions similar among different pairs of competitively inhibiting molecules?
APPENDIX: BASIC RASMOL COMMANDS
TRANSLATION
(to move a molecule in the X-Y PLANE):
Click mouse button and drag
ROTATION
Drag mouse
ZOOM (to magnify or reduce in size)
Press Shift key and drag mouse